NeuroscienceMar 15, 2025

Gut nerve system problems linked to brain disorders: The overlooked brain in neurological diseases

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

The Enteric Nervous System (ENS) is implicated in neurodegenerative and neurodevelopmental disorders such as Parkinson's disease and autism spectrum disorder.

ENS functions autonomously while communicating with the central nervous system through the gut-brain axis.
Dysfunction in the ENS is associated with disrupted neurotransmission, gut microbiota imbalance, and neuroinflammation, contributing to disease development.
The gut-brain axis allows for communication that influences both gut health and neurological function.
Conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are linked to ENS dysregulation, affecting both systemic and central nervous system health.
Emerging therapeutic strategies targeting ENS dysfunction include prebiotics, probiotics, fecal microbiota transplantation, and vagus nerve stimulation.

Simplified

The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Gut nerve system problems linked to brain disorders: The overlooked brain in neurological diseases

Abstract

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Abstract

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You found one interesting study. We’ll send the next 7.

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Recent issues from the gut-brain axis brief